ADVANCED PSYCHOPHARMACOLOGY
Psychology 572 Spring, 2005
Dr. John M. Morgan Tuesday & Thursday, 8am to 9:20
Natural Resources 201
April E. Nichols
History of Coffee
Our love affair with coffee did not begin with the advent of Starbuck's.
As a matter fact, America's May/December romance with this beverage
is rather recent in light of coffee's long history.
It is believed that caffeine yielding plants were discovered 600,000 to
700,00 years ago during the Stone Age (History of Caffeine). It is likely
that ancient people chewed the seeds and barks of these plants and
soon grew to associate them with changes in mood and behavior.
Eventually, coffee was cultivated and eaten to increase energy,
stimulate mood, and sharpen awareness (History of Caffeine).
Originally it may have been ground into a paste, or the berries
themselves may have been eaten. Later, it was discovered that by
steeping it into a hot liquid that it's stimulating effects were
heightened (History of Caffeine).
The first written evidence of coffee appeared in Arab documents in the
10th century; however, there is evidence that coffee plants were
cultivated for the consumption of their berries as early as the 6th
century in Ethiopia (History of Coffee).
Arab legend recounts the story of a young East African goatherd who
discovered the stimulant properties of the berries when his goats
consumed the berries and became quite frisky. Coffee berries are still
being chewed in Northern Africa today (History of Coffee).
Eventually, monks transported the dried berries to distant monasteries
where they eventually made their way to the Arabian Peninsula. The
Arabs began cultivating the plants for their own use and were the first
to boil the beans to create a drink called "qahwa", literally, "that
which prevents sleep" (History of Coffee).
The Arab's monopoly on coffee ended when it was introduced to
Constantinople by the Ottoman Turks in the 15th century (Coffee
Timeline). The Turks were the first to roast the beans over an open
fire. The roasted beans were then crushed and boiled in water to
produce a crude version of the coffee that we enjoy today (Coffee
Universe). In addition, the Turks often added spices such as cinnamon
and cardamom to enhance its flavor (Coffee Timeline). The first coffee
shop, Kiva Han, was opened in Constantinople in 1475 (Coffee
Universe).
Coffee arrived in Europe in the 17th century via the Venetian trade
merchants (Coffee Timeline). The Catholic Church condemned coffee
as "the drink of the devil", but Pope Clement VIII found the taste of
coffee much to his liking and ended up "baptizing" the drink instead,
making it morally acceptable to Christians (History of Coffee).
Eventually, coffee spread throughout Europe with the first coffee
houses opening in Italy, France, and England by the mid 17th century.
Coffee also reached the colonies in North America by way of
Jamestown, Virginia in 1607(Coffee Timeline).
During this same time, coffee found it's way to the Americas through a
small hardy plant nurtured by a French infantry captain on his way
across the Atlantic (Coffee Universe). Transplanted to the island of
Martinique in the Caribbean, this one plant yielded over 19 million
trees in the span of 50 years time (History of Coffee). From here,
coffee spread rapidly through the rest of Central and South America.
At the end of the 17th century, the Dutch became the first to cultivate
coffee commercially in Ceylon as well as their colony in Java.
Eventually, commercial cultivation spread to Brazil and by the first
part of the 20th century, Brazil was harvesting nearly 90% of the
world's coffee (Coffee Timeline).
Today, coffee is a global industry that employs more than 20 million
people and ranks second only to petroleum in terms of dollars traded
on the world market. Coffee remains a profitable export for small
farmers in developing countries. Coffee is the world's most popular
beverage with over 400 million cups consumed each year. Currently,
the United States consumes and exports 75% of the world's coffee.
Since the first Starbuck's opened in 1971 in Seattle, Washington, the
sale of specialty coffees is rising annually in this country with sales
reaching well into the multi-billion dollar range (History of Coffee).
Current Research
Caffeine is the most commonly ingested psychoactive substance in
the world and is naturally found in tea, coffee, and cocoa (Pendergrast,
1999). Additionally, 70% of all the soft drinks consumed in this
country contain caffeine and 80% of Americans over the age of 20
report consuming caffeine on a daily basis (New York Times, 1997).
Caffeine is a legal stimulant and is readily available to adults and
children alike (Bernstein, Carroll, Thuras, Cosgrove, & Roth, 2002).
As you might imagine, there is a myriad of research on the
physiological and behavioral effects of caffeine on adults, however,
there has been little research concerning caffeine dependency in
children and adolescents. A recent study (Bernstein et. al., 2002)
examined 36 adolescents 13 to 17 who were daily consumers of
caffeine. The level of their dependence was assessed based on the
American Psychological Association's Diagnostic and Statistical
Manual of Mental Disorders (DSM IV) substance dependence criteria:
tolerance, withdrawal, unsuccessful attempts to reduce or limit use,
and continued use despite recurring physical or psychological
problems. If more than one of these symptoms was reported during
screening, the adolescent was eligible for participation in the study.
Based on these criteria, 41.7% of the participants reported tolerance,
77.8% endorsed withdrawal symptoms after quitting or cutting back on
caffeine, 38.9% reported persistent cravings or difficulties in
controlling use, and 16.7% reported continued caffeine usage despite
accompanying physical and psychological problems. Overall, 22.2%
met the definition for caffeine dependence based on meeting three out
of four of the DSM IV criteria (Bernstein, et. al., 2002).
Those participants in the current study, who abused or were
dependent on marijuana, also had a significantly higher daily
consumption of caffeine than those who were not. Other studies have
shown a similar relationship between high caffeine consumption
before age 12 and alcohol dependence. Also, participants in the
current study who were nicotine dependent were also shown to have
consumed more daily caffeine than those who were not nicotine
dependent (Bernstein et. al., 2002). This may in part be explained by
the fact that nicotine speeds up the metabolism of caffeine in the body
which is why teen smokers who drink coffee drink so much more of it
than non-smokers. In terms of mood, the caffeine dependent group
also reported significantly higher levels of depression and anxiety than
the non-dependent group (Bernstein et. al., 2002).
Although arguably the sample size for this study was small, the
significance of the results certainly raise questions regarding
caffeine's potential to facilitate other substance taking behavior
including nicotine, marijuana, and alcohol. Further exploration of the
possibility that caffeine may precede other drug use certainly seems
warranted.
Another interesting study (Fillmore, Roach, & Rice, 2002) looks at
expectancy regarding the impairing behavioral effects of alcohol and
caffeine's ability to counteract those effects. Substance expectancy
can be defined as how a person interprets or perceives the effects of a
particular substance based on their previous relationship and
experiences with that substance (Kirsch, 1999). It has been well
established that drinkers who assume alcohol to exert strong
performance impairing effects often develop a compensatory response
where performance often appears to be at near sober levels (Fillmore
et. al., 2002). This particular study tested the hypothesis that drinkers
who expected caffeine to counteract the impairing performance
effects of alcohol would be less likely to develop the compensatory
response, and consequently their behavior would show even greater
impairment than those drinkers that did not expect caffeine to have
that effect. Put simply, those drinkers who were expecting a few cups
of strong coffee to sober them up before they grabbed their keys and
drove home would not make any compensatory adjustments in their
psychomotor behavior.
Participants included 23 men and 19 women between the ages of 21
and 32 years. Anyone who reported a psychiatric or substance use
disorder, head trauma or other central nervous system injury was
excluded. Also, participants with recent drug use were also excluded
from the study. The Blood Alcohol Concentration produced to observe
these expectancy effects peaked on average at 80mg/dl. This is the
standard concentration used to prosecute drunk drivers throughout
most of the United States (Fillmore et. al., 2002).
The participants were divided into four expectancy groups and all
received a moderate dose of alcohol. Two of the groups were led to
believe that coffee would counteract the effects alcohol and within
this group, one group received caffeine and the other received a
placebo. The other two groups were led to expect no counteracting
effects of caffeine and again, one group was given caffeine and the
other was given a placebo. There were also two control groups and
one group received alcohol and the other an alcohol placebo. The
control groups were given no information about their treatment
condition, particularly in regards to the impairing effects of alcohol
(Fillmore et. al., 2002).
The results of the study supported the researchers' hypothesis and the
joint expectancy relationship was upheld. Those participants who had
strong expectations of alcohol's performance impairing effects as well
as the expectancy of caffeine to counteract those effects did not
display the compensatory response and showed greater levels of
impairment than those participants who did not have the caffeine
expectancy This held true whether they had received the caffeine or a
caffeine placebo (Fillmore et. al., 2002). The differences between the
two expectancy groups could not be attributed to Blood Alcohol
Concentration, psychomotor skills, drinking habits, or caffeine
consumption. Also interesting is the fact that the expectancy effect
was specific to psychomotor impairment only and had no effect on the
participants' subjective perception of intoxication (Fillmore et. al.,
2002).
This study illustrates the importance of understanding the interactions
between expected and actual pharmacological effects of caffeine and
other substances and how expectancies have the potential to either
reduce or intensify the impairing effects of certain substances such as
alcohol (Fillmore et. al., 2002). In light of this particular study, the
myth of sobering up with a few cups of coffee is not only false but also
quite dangerous.
A final study (Larsen and Carey, 1998) looks at previous and current
research on the use and abuse of caffeine in mental health settings.
Mental health patients consume more caffeine on average than the
rest of the general population in the United States (Larson and Carey,
1998). One study of 21 psychiatric outpatients suggests that mental
health patients may consume as much as seven times more caffeine
than individuals in the general population (Larson and Carey, 1998).
Another study of 100 inpatients describes the highest consumption
levels to be as much as 14.4 cups of coffee per day as compared to an
average of 1 to 2 cups daily for the general population Koczapski,
Paredes, Kogan, Ledwidge, & Higenbottam, 1989). Several other
studies describe means between 4.5 cups to 9.44 cups per day with
some patients reporting as many as 65 cups per day (Hamera,
Schneider, & Deviney, 1995; James, Crosbie, & Paull, 1987)!
High levels of caffeine consumption among mental health patients is
significant because it can exacerbate a psychotic state, increase
panic attacks and manic episodes, as well as cause behaviors that
may be confused with the hallucinatory symptoms of Schizophrenia
(Greden, 1974). Caffeine also reduces the effectiveness of certain
medications and has dangerous interactions with others. Some
common forms of medications adversely effected by caffeine are
lithium salts used to treat Bipolar Disorder, monoamine oxidase
inhibitors (MAOIs) often prescribed for depression, selective serotonin
reuptake inhibitors (SSRIs) most commonly prescribed for depression,
and certain antipsychotic medications (Larson and Carey, 1998).
Caffeine also competes for the same receptor sites in the brain as
several antipsychotic medications thus rendering them nearly
ineffective (Kirmer, 1988).
Why mental health patients consume larger amounts of caffeine is not
completely understood. Some theories suggest that psychiatric
patients may be self-medicating to counteract the symptoms of severe
depression while others hypothesize that it may be to counteract the
unpleasant effects of large doses of certain psychotropic medications.
These as well as several other interesting theories remain largely
unexplored (Schneier and Siris, 1987; Khantzian, 1985).
Due to the potentially dangerous interaction of high caffeine
consumption with certain medications, it would seem that caffeine
assessment throughout a mental health patient's course of treatment
would be recommended. At the very least, high levels of caffeine
complicate treatment and at worst, have potentially devastating
repercussions on treatment outcome.
References
American Psychiatric Association, (1994). Diagnostic and Statistical
Manual of Mental Disorders (DSM IV), 4th ed., New York: American
Psychiatric Association.
Bernstein, G.A., Carroll, M.E., Thuras, P.D., Cosgrove, K.P., & Roth,
M.E., (2002). Caffeine Dependence in Teenagers. Drug and Alcohol
Dependence, 66, 1 to 6.
Fillmore, M.T., Roach, E.L., & Rice, J.T., (2002). Does caffeine
counteract alcohol induced impairment? The Ironic Effects of
Expectancy. Journal of Studies in Alcohol, (63), 745 to 754.
Greden, JlF. (1974). Anxiety of caffeinism: A diagnostic dilemma.
American Journal of Psychiatry, 131, 1089 to 1092.
Hamera, E., Schneider, J.K., & Deviney, S. (1995). Alcohol, cannabis,
nicotine, and caffeine use and symptoms distress in Schizophrenia.
Journal of Nervous and Mental Diseases, 183, 559 to 565.
History of Caffeine, (n.d.) Retrieved January 24, 2005 from
http://www.k12.n.f.ca?cms/DrugsOnline/caffeine/.html.
History of Coffee, (n.d.). Retrieved February 20, 2005, from
http://www.coffeeuniverse.com/university_hist.html.
James, J.E., Crosbie, J., & Paull, I. (1987). Symptomatology of habitual
caffeine use amongst psychiatric patients. Australian Journal of
Psychology, 39, 139 to 149.
Khantzian, E.J. (1985). The selfmedication hypothesis of addictive
disorders: Focus on heroin and cocaine dependence. American Journal
of Psychiatry, 142, 1259 to 1264.
Kirmer, D.A., (1988). Caffeine use and abuse in psychiatric clients.
Journal of Psychosocial Nursing, 26, 20 to 25.
Kirsch, I. (1999). How expectancies shape experience. Washington
D.C., American Psychological Association.
Koczapski, A., Paredas, J., Kogan, C., Ledwidge, B., & Higgenbottam,
J., (1989). Effects of caffeine on behavior of Schizophrenic inpatients.
Schizophrenia Bulletin, 15, 339 to 344.
Larson, C.A., & Carey. K.B., (1998). Caffeine: Brewing trouble in mental
health settings. Professional Psychology: Research and Practice,
28(4), 373 to 376
New York Times, August 22, 1997. More hip, higher hop caffeinated
drinks catering to excitable boys and girls.
Pendergast, M., (1999). Uncommon grounds: The history of coffee and
how it transformed our world, New York: Basic Books.
Schneier, F.R., & Siris, S.G. (1987). A review of psychoactive
substance use and abuse in Schizophrenia: Patterns of drug choice.
Journal of Nervous and Mental Disease, 175, 641 to 652
Shapiro, M., (1994, Dec.). Coffee Timeline. Retrieved February 20,
2005 from http://www.telusplanet.net/public/coffee/history.htm
Brian Lok
Caffeine Chemistry
Caffeine is in a class of chemicals known as alkaloids. The exact
definition of an alkaloid will depend on whom you talk to, but in
general they are any number of colorless, complex and bitter organic
bases containing nitrogen and usually oxygen that occur in plants and
frequently have significant pharmacological activity. The term
'alkaloid' was first coined by the German pharmacist Friedrich
Serturner while working with opium (Pendell, 1995). He isolated a
substance which reacted chemically like a base and since bases are
sometimes called alkalis (Zumdahl et. al., 2003) he named it an
alkaloid. Incidentally he named this, the first alkaloid ever discovered,
morphine after the god of dreams Morpheus. More specifically, an
alkaloid is usually a nitrogen containing compound of plant origins
which has a complex molecular structure with the nitrogen atom
involved in a heterocyclic ring. It should be noted that some
authorities do not consider the purines, a class of nitrogen containing
heterocyclics of which caffeine is a member, to be an alkaloid at all
though it is a heterocyclic nitrogenous base (Pelletier, 1970). A
heterocyclic ring is a compound (i.e., group of atoms) in which all the
atoms in the ring are not alike, or not the same atom (Hein et. al.,
1993).
Caffeine is the common name for 1,3,7 trimethylxanthine, which is
another name for 1,3,7 trimethyl 2,6 dioxopurine.
(As per instructions, document does not contain required hyphens.)
The chemical names above are named in a systematic manner based
on their particular molecular structure using the internationally
recognized and agreed upon IUPAC system. IUPAC is an acronym for
the International Union of Pure and Applied Chemistry. This system
was developed so scientists could use a single name to deduce the
chemical structure of a compound. In order to be able to name organic
chemical compounds (organic chemistry is just the study of carbon
containing compounds) you need some knowledge of certain common
chemical groups. The more you know, the shorter the names can
become; for instance 2,6 dioxopurine is the xanthine molecule. To get
the structure from the name, work 1,3,7 trimethyl 2,6 dioxopurine
backwards. The main body of the caffeine molecule is based on the
purine ring:
Figure 1
The purine ring system is widely distributed in nature although the
actual purine molecule itself is not encountered. Attached to the
purine ring is two (di) oxygen (oxo) molecules (O for 'oxygen') at the
locations 2 and 6.
Figure 2
The way these points of attachments are numbered are basically
memorized, along with the basic chemical structures (like purine,
benzene and hexane), but rules do exist to aid in figuring them out.
Finally, the caffeine molecule also has three (tri ) methyl groups [the
methyl group is CH3, or 1 carbon atom (C is for 'carbon') attached to 3
hydrogen atoms (H is for 'hydrogen')] attached to the purine ring at the
specific remaining points.
Figure 3
Caffeine is a white in its pure state. It melts at a temperature of 236
degrees Celsius. It typically does not get a chance to melt though, as
it sublimes (transforms from a solid state directly to a gaseous state)
at 178 degrees Celsius (Clarke et.al.). Purines in general are relatively
insoluble (unable to dissolve) in water at physiological pH (pH is a
measure of a solutions acidity), but caffeine becomes more soluble at
higher temperatures (Clarke et.al.).
Caffeine Route of Access
The usual route that caffeine is administered is orally. Other
absorption routes include rectally, in the form of enemas and
insufflating (i.e. snorting) caffeine U.S.P. intranasally (Pendell, 2002).
When taken orally, caffeine is completely and rapidly absorbed with
significant blood levels being reached in 30 to 40 minutes and
complete absorption over the next 90 minutes (Julien, 2001). Blood
plasma levels peak at about a one half to 1 hour and begin to decrease
with a half life of 3 to four hours (Keltner et. al., 1997). Caffeine
distributes in almost equal concentrations throughout the total body
water. It passes both the blood brain barrier and the placental tissue
and will show up in breast milk (Keltner et. al., 1997). Once in the
blood stream, the caffeine will begin to take its effects.
References
Clarke, R.J., Macrae, R., (n.d.). Coffee. Vol. 1: Chemistry. Elseveir
Applied Science Publishers LTD, Essex, England.
Hein, M., Best, L. Pattison, S. and Arena, S. (1993). Introduction to
Organic and Biochemistry. Wadsworth, Inc., Belmont, CA.
Julien, Robert M., (2001). A Primer of Drug Action: A Concise,
Nontechnical Guide to the Actions, Uses, and Side Effects of
Psychoactive Drugs. WH Freeman/Owl Books, new York.
Keltner, Norman L., Folks, David G. (1997). Psychotropic Drugs: 2nd ed.
Mosby/Year Book, Inc., St. Louis, MS.
Palfai, T., & Jankiewicz, H. (2001). Drugs and human behavior. McGraw
Hill Primis:New York.
Pelletier, S.W. (1970). Chemistry of the Alkaloids. Reinhold Book
Corporation, New York, NY.
Pendell, Dale. (1995). Pharmako/Poeia: Plant powers, Poisons and
Herbcraft. Mercury House Books, San Francisco,
CA.
Pendell, Dale. (2002). Pharmako/Dynamis: Stimulating Plants, Potions
and Herbcraft. Mercury House Books, San Francisco, CA.
Zumdahl, S.S., Zumdahl, S.A, (2003). Chemistry, 6th ed. Houghton
Mifflin Company, Boston, MA.
Jessica
Caffeine as an antagonist
Adenine and guanine are two purine bases found in the body
(Fredholm, B.B., Battig, K., Holmen, J., Nehlig, A., & Zvartau, E.E.,
1999). These two bases are the key components of DNA and RNA.
Adenosine is an adenine molecule and a naturally present depressant
in the body, with its own receptors. Adenosine has several functions
including inhibiting the release of transmitters in the central nervous
system (CNS), slowing the firing rate of CNS neurons and pacemaker
cells, and enhancing the contractions of smooth intestinal and blood
vessel muscles (Palfai, T., And Jankiewicz, H.,2001).
The Chemical structure between the adenine molecule and the
caffeine molecule is similar enough that caffeine can fit into
adenosine receptors, but it cannot stimulate them. So, caffeine
becomes an antagonist of adenosine receptors, whose main action is
to compete with adenosine to occupy the adenosine receptors. Once
caffeine is in the stomach, it travels quickly to the brain and does
what adenosine normally does; it binds to the adenosine nerve
receptors. Once bound to the adenosine receptors, caffeine speeds up
cellular activity, the opposite of the slowing down (sleepy) effects that
occur when adenosine binds to the adenosine receptors.
Caffeine has other potential pharmacological affects aside from
blocking adenosine receptors. With extremely high (millimolar)
concentrations, caffeine has the potential to inhibit cyclic nucleotide
phosphodiesterase molecules, block the inhibitory neurotransmitter
GammaAminoButyric Acid (GABA) receptors, and mobilize intracellular
calcium (Taketo, M., Matsuda, H., & Yoshioka, T, 2004). However,
caffeine's primary direct action is blocking adenosine receptors and
indirectly acting upon the receptors for neurotransmitters. There are
four adenosine receptors classified as A1, A2a, A2b, and A3. Only the
first two subtypes are important for neurotransmitters because
subtypes A2b and A3 are located mostly in peripheral tissues outside
of the brain (Fredholm, B.B., Arslan, G., Kull, B., & Svenningsson,
1998).
A1 receptors are the most abundant of the four subtypes (Fredholm,
B.B., et al, 1999). They are primarily abundant in the cerebral cortex,
hippocampus, cerebellum, and the reticular formation of the spinal
cord. When adenosine accumulates at A1 receptors, the release of
most of the brain neurotransmitters (e.g., glutamate, GABA,
norepinephrine, serotonin, and acetylcholine), are inhibited. A1
receptors inhibit the enzyme adenylyl cyclase, block presynaptic
calcium channels, and activate potassium channels. Generally stated,
A1 adenosine receptors inhibit neural activity.
A2 receptors activate adenlyl cyclase, which can inhibit calcium
channels (Fredholm, B.B., et al., 1998). Only the A2a subtype of the A2
receptors is significantly active. The A2a receptors are located mainly
in the basal ganglia (area of the brain controlling locomotion). Activity
of the A2a receptor inhibits locomotor activity. Adenosine A2a
receptors are prominent in endothelial cells, which results in the
ability of adenosine to dilate cerebral blood vessels. When caffeine
binds to this receptor rather than adenosine, it conversely has the
possible effect of constricting cerebral blood vessels, thus relieving
headaches.
The antagonist effect of caffeine on the A2a receptor inhibits GABA
release. This can neutralize the effects of drugs that work to enhance
the effect of GABA (e.g., benzodiazepines). Caffeine does not activate
dopamine release in the nucleus accumbens, an activity associated
with addiction. The properties of addiction associated with caffeine
are connected entirely to withdrawal symptoms. The general effect of
caffeine is to increase neural activity in the brain. This is the opposite
of the general effect of adenosine, which is to inhibit neural activity,
thus promoting sleepiness.
Physiological changes
Caffeine is a psychomotor stimulant that leads to whole body changes
through its neuronal activity in the central nervous system (CNS).
Once in the body, caffeine is distributed to all body fluids and tissues,
but has a low percentage of binding to these tissues (Pafai, T, &
Jankiewcz, H, 2001).Caffeine causes skeletal muscle to contract and
smooth muscle to relax. It also can significantly increase the
secretion of gastric acid and pepsin in the stomach. Coffee
particularly has this significant effect on gastric secretion.
Caffeine can increase levels of free fatty acids in the blood plasma to
be twice as high as normal (Thomas, C.L., 1997). Caffeine can also
elevate levels of cortisol and epinephrine. It is suggested that elevated
epinephrine and free fatty acids due to caffeine consumption may
cause a decrease in insulin sensitivity (Akiba, T. et al, 2004). This may
lead to a possible blood glucose increase (Thomas, C.L., 1997).In the
CNS, caffeine stimulates the respiratory center in the medulla and it
stimulate the cortex.
Caffeine stimulates the heart by increasing blood flow, oxygen, and
strength of the heart muscles during contraction (Pafai, T., &
Jankiewick, H., 2001). Caffeine increases blood pressure and
respiratory rate, and decreases heart rate (Papadeli et al., 2002;
Quinlan et al., 2000). One study testing the effects of caffeine on the
CNS and cardiorespiratory system in human subjects found that as the
subjects dose of caffeine increased, so did their optimal task
performance, and with these increases, blood pressure and respiratory
rate were adversely affected (Papadeli et al., 2002).
Blood pressure changes occur because caffeine affects the peripheral
blood vessels through stimulation of the autonomic nuclei. Caffeine
can cause the peripheral blood vessels to dilate while restricting those
blood vessels in the brain (Fredholm et al., 1999). The vasoconstriction
of the vessels due to caffeine usage is why caffeine is sometimes used
to treat migraine headaches.
Like most chemicals taken into the body, caffeine is metabolized in
the liver (Pafai, T, & Jankiewicz, H, 2001). The rate at which caffeine
is metabolized depends upon individual factors such as diet, smoking,
pregnancy, oral contraceptive use, age, the presence of disease,
genetic variance, ethnicity, and gender. Caffeines final destination is
its excretion through the kidneys.
References
Akiba et al. (2004). Inhibitory mechanism of caffeine on insulin-
stimulated glucose uptake in adipose cells. Biochemical
Pharmacology, 68, 192 to 1937.
Fredholm, B., Arslan, G., Kull, B., & Svenningsson, P. (1998). Locating
the neuronal targets for caffeine. Drug Development Research, 45, 324
to 328.
Fredholm, B., Battig, K., Holmen, J., Nehlig, A., & Zvartau, E. (1999).
Actions of caffeine in the brain with special reference to factors that
contribute to its widespread use. Pharmacological Reviews, 51, 8 to
133.
Palfai, T., & Jankiewicz, H. (2001). Drugs and human behavior. McGraw
Hill Primis:New York.
Papadeli, C., Papadelis, C., Louizos, A., & Tziampiri, O. (2002).
Maximum cognitive performance and physiological time trend
measurements after caffeine intake. Cognitive Brain Research, 13, 40
to 415.
Quinlan, P. et al. (2000). The acute physiological and mood effects of
tea and coffee: The role of caffeine level. Pharmacology Biochemistry
and Behavior, 66, 1 to 28.
Jessica
Caffeine as an antagonist
Adenine and guanine are two purine bases found in the body
(Fredholm, B.B., Battig, K., Holmen, J., Nehlig, A., & Zvartau, E.E.,
1999). These two bases are the key components of DNA and RNA.
Adenosine is an adenine molecule and a naturally present depressant
in the body, with its own receptors. Adenosine has several functions
including inhibiting the release of transmitters in the central nervous
system (CNS), slowing the firing rate of CNS neurons and pacemaker
cells, and enhancing the contractions of smooth intestinal and blood
vessel muscles (Palfai, T., And Jankiewicz, H.,2001).
The Chemical structure between the adenine molecule and the
caffeine molecule is similar enough that caffeine can fit into
adenosine receptors, but it cannot stimulate them. So, caffeine
becomes an antagonist of adenosine receptors, whose main action is
to compete with adenosine to occupy the adenosine receptors. Once
caffeine is in the stomach, it travels quickly to the brain and does
what adenosine normally does; it binds to the adenosine nerve
receptors. Once bound to the adenosine receptors, caffeine speeds up
cellular activity, the opposite of the slowing down (sleepy) effects that
occur when adenosine binds to the adenosine receptors.
Caffeine has other potential pharmacological affects aside from
blocking adenosine receptors. With extremely high (millimolar)
concentrations, caffeine has the potential to inhibit cyclic nucleotide
phosphodiesterase molecules, block the inhibitory neurotransmitter
GammaAminoButyric Acid (GABA) receptors, and mobilize intracellular
calcium (Taketo, M., Matsuda, H., & Yoshioka, T, 2004). However,
caffeine's primary direct action is blocking adenosine receptors and
indirectly acting upon the receptors for neurotransmitters. There are
four adenosine receptors classified as A1, A2a, A2b, and A3. Only the
first two subtypes are important for neurotransmitters because
subtypes A2b and A3 are located mostly in peripheral tissues outside
of the brain (Fredholm, B.B., Arslan, G., Kull, B., & Svenningsson,
1998).
A1 receptors are the most abundant of the four subtypes (Fredholm,
B.B., et al, 1999). They are primarily abundant in the cerebral cortex,
hippocampus, cerebellum, and the reticular formation of the spinal
cord. When adenosine accumulates at A1 receptors, the release of
most of the brain neurotransmitters (e.g., glutamate, GABA,
norepinephrine, serotonin, and acetylcholine), are inhibited. A1
receptors inhibit the enzyme adenylyl cyclase, block presynaptic
calcium channels, and activate potassium channels. Generally stated,
A1 adenosine receptors inhibit neural activity.
A2 receptors activate adenlyl cyclase, which can inhibit calcium
channels (Fredholm, B.B., et al., 1998). Only the A2a subtype of the A2
receptors is significantly active. The A2a receptors are located mainly
in the basal ganglia (area of the brain controlling locomotion). Activity
of the A2a receptor inhibits locomotor activity. Adenosine A2a
receptors are prominent in endothelial cells, which results in the
ability of adenosine to dilate cerebral blood vessels. When caffeine
binds to this receptor rather than adenosine, it conversely has the
possible effect of constricting cerebral blood vessels, thus relieving
headaches.
The antagonist effect of caffeine on the A2a receptor inhibits GABA
release. This can neutralize the effects of drugs that work to enhance
the effect of GABA (e.g., benzodiazepines). Caffeine does not activate
dopamine release in the nucleus accumbens, an activity associated
with addiction. The properties of addiction associated with caffeine
are connected entirely to withdrawal symptoms. The general effect of
caffeine is to increase neural activity in the brain. This is the opposite
of the general effect of adenosine, which is to inhibit neural activity,
thus promoting sleepiness.
Physiological changes
Caffeine is a psychomotor stimulant that leads to whole body changes
through its neuronal activity in the central nervous system (CNS).
Once in the body, caffeine is distributed to all body fluids and tissues,
but has a low percentage of binding to these tissues (Pafai, T, &
Jankiewcz, H, 2001).Caffeine causes skeletal muscle to contract and
smooth muscle to relax. It also can significantly increase the
secretion of gastric acid and pepsin in the stomach. Coffee
particularly has this significant effect on gastric secretion.
Caffeine can increase levels of free fatty acids in the blood plasma to
be twice as high as normal (Thomas, C.L., 1997). Caffeine can also
elevate levels of cortisol and epinephrine. It is suggested that elevated
epinephrine and free fatty acids due to caffeine consumption may
cause a decrease in insulin sensitivity (Akiba, T. et al, 2004). This may
lead to a possible blood glucose increase (Thomas, C.L., 1997).In the
CNS, caffeine stimulates the respiratory center in the medulla and it
stimulate the cortex.
Caffeine stimulates the heart by increasing blood flow, oxygen, and
strength of the heart muscles during contraction (Pafai, T., &
Jankiewick, H., 2001). Caffeine increases blood pressure and
respiratory rate, and decreases heart rate (Papadeli et al., 2002;
Quinlan et al., 2000). One study testing the effects of caffeine on the
CNS and cardiorespiratory system in human subjects found that as the
subjects dose of caffeine increased, so did their optimal task
performance, and with these increases, blood pressure and respiratory
rate were adversely affected (Papadeli et al., 2002).
Blood pressure changes occur because caffeine affects the peripheral
blood vessels through stimulation of the autonomic nuclei. Caffeine
can cause the peripheral blood vessels to dilate while restricting those
blood vessels in the brain (Fredholm et al., 1999). The vasoconstriction
of the vessels due to caffeine usage is why caffeine is sometimes used
to treat migraine headaches.
Like most chemicals taken into the body, caffeine is metabolized in
the liver (Pafai, T, & Jankiewicz, H, 2001). The rate at which caffeine
is metabolized depends upon individual factors such as diet, smoking,
pregnancy, oral contraceptive use, age, the presence of disease,
genetic variance, ethnicity, and gender. Caffeines final destination is
its excretion through the kidneys.
References
Akiba et al. (2004). Inhibitory mechanism of caffeine on insulin-
stimulated glucose uptake in adipose cells. Biochemical
Pharmacology, 68, 192 to 1937.
Fredholm, B., Arslan, G., Kull, B., & Svenningsson, P. (1998). Locating
the neuronal targets for caffeine. Drug Development Research, 45, 324
to 328.
Fredholm, B., Battig, K., Holmen, J., Nehlig, A., & Zvartau, E. (1999).
Actions of caffeine in the brain with special reference to factors that
contribute to its widespread use. Pharmacological Reviews, 51, 8 to
133.
Palfai, T., & Jankiewicz, H. (2001). Drugs and human behavior. McGraw
Hill Primis:New York.
Papadeli, C., Papadelis, C., Louizos, A., & Tziampiri, O. (2002).
Maximum cognitive performance and physiological time trend
measurements after caffeine intake. Cognitive Brain Research, 13, 40
to 415.
Quinlan, P. et al. (2000). The acute physiological and mood effects of
tea and coffee: The role of caffeine level. Pharmacology Biochemistry
and Behavior, 66, 1 to 28.
Jim Dimke
Effects of Human Performance and Behavior
Upon taking 100 to 200 milligrams of caffeine
typically the following takes place: "greater sustained
intellectual effort and a more perfect association of
ideas," as well as "a keener appreciation of sensory
stimuli" (Ritchie, 1975). However, there is very little
evidence that is supported by research that states that
changes of this nature actually take place. These ideas
are most certainly surrounded by the culture associated
with coffee and caffeine intake. Studies have shown that
people think they are performing better due to caffeine,
when there performance level actually showed no improvement
in the given tasks.
Research has shown that moderate doses of caffeine can
significantly increase visual sensitivity in regards to
light as well as increase the speed of auditory reaction
time (Dews, 1984). Studies have simulated tasks such as
driving and flight simulators and the same results hold
true, however, we need to keep in mind that replicating
these tasks is difficult. Most research has determined
that the effects of caffeine depend on many factors
including: individual susceptibility, dose, time of
consumption, and the nature of the task (James, 1991). It
is also important to note caffeine's affect on fatigue.
The main effedt of caffeine was to reduce the effect of
drowsiness and boredom. It was noted by Wess and Laties
(1962) that caffeine caused an improvement in the mood of
subjects and a better attitude toward their tasks. Mood
change, however, cannot be attributed to the caffeine as it
may be due to the improvement in performance. Either way,
it seems that it would be a good idea for employers to
endorse a consistent schedule of coffee breaks.
Athletic Performance
Results are far from consistent but caffeine taken in
doses of 10mg/kg (700mg for a 155 pound person) has been
known to improve performance in events that require
endurance. For example, people will not benefit in tasks
like weight lifting but cross-country runners and skiers
will benefit from taking caffeine. Again, these results
have been inconsistent. Although there is not a consistent
significant finding that caffeine increases athletic
performance, caffeine is still a drug that is monitored by
the International Olympic Committee. Caffeine in
concentrations in the urine higher than 15mg/1 is
considered a disqualifying factor but then again, it would
take about 15 cups of coffee to achieve this.
Effects on Sleep
Caffeine is the major ingredient in many over the
counter stimulant pills (most containing about 100mg of
caffeine). With that in mind, it is safe to say that there
is little doubt that caffeine can produce insomnia.
Caffeine has also been know to increase the sensitivity to
sound and light; that is people wake up more easily in
response to a sound or a flash of light during the night.
Although the frequency and duration of REM is not altered
upon the intake of caffeine, it has been supported that
there is an increase in the percent of time spent in stage
2 sleep (light sleep) and decreases in stage 3 and 4 sleep
(deep sleep). Participants in these studies reported
sleeping less soundly and were less rested (Bonnet & Arand,
1992).
Effect on Behavior of Nonhumans
Caffeine has been known to have effects on nearly
every animal species. It has a reputation for giving the
mind and the body a boost. An experiment was conducted
with rats running mazes. It was discovered that the rats
that ingested caffeine learned solutions to the maze faster
and remembered them better. Darnes and Elthrington (1973)
also reported some rats dying due to convulsions as well as
bleeding as a result of attacking themselves. Can you
imagine if humans metabolized caffeine the same way that
some animals do?
Subjective Effects
Early studies of caffeine were confusing. While some
studies reported increased anxiety, jitteriness, and
nervousness, other studies reported no subjective effects
at all. Recently studies have shown that subjects
experience feelings of well-being, alertness, energy,
motivation for work and self-confidence (Rush, Sullivan, &
Griffiths, 1995). It should be noted that both Griffiths
and Mumford stated that a restricted set of conditions are
required for people to experience positive effects. It is
also reported that individuals tend to experience positive
effects when they are given low doses such as 20 to 200mg.
Higher doses of caffeine are more likely to cause
unpleasant effects such as anxiety, confusion, and the
occasional jitters. I'd like to add that in my very
limited experience as a practicum student therapist I have
seen many cases of anxiety disorders that have in some way
or another involved caffeine. On a more positive note
there is no evidence to suggest that caffeine consumption
increases our risk of heart, lung, or kidney disease.
References:
McKim, W.(1997). Drugs and behavior: An Introduction to
behavioral pharmacology(3rd Ed.)New Jersey, Prentice Hall
Phelan,J. & Burnham, T. (2002). Mean genes: From sex to
money to food: taming our primal instincts. New York,
Random House
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Copyright © 2005, Dr. John M. Morgan, All rights reserved -
This page last edited 02-23, 2004
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